The Cell Morphology Core (CMC) laboratory has been constructed to meet the increasing demands of cell biology and transgene detection in the area of gene therapy research. John Tazelaar, M.D., a board certified pathologist, serves as Assistant Director in charge of the CMC. Routine morphology support in the form of paraffin, frozen, and glycolmethacrylate (GAMA) sectioning for light microscopy as well as standard transmission electron microscopy (TEM) are provided as comprehensive services to investigators participating in P01 projects. In addition, the core emphasizes state-of- the-art methodologies for detecting transgene expression including in situ hybridization, immunocytochemistry, and histochemical detection of beta- galactosidase and alkaline phosphatase reporter genes. The Cell Morphology Core provides techniques of in situ hybridization and immunocytochemical detection of transgenes as comprehensive services. Principal Investigators of this P01 application anticipate heavy utilization of the Cell Morphology Core in several areas. Dr. Wilson, Principal Investigator of Project 1, will utilize immunohistochemistry and in situ hybridization to detect transgene expression following direct injection of AAV vectors. He will also seek the help of the Core in analyses of tissues for inflammatory and immunological responses. Dr. Sweeney, Principal Investigator of Project 2, requires use of the Core in the detection of his transgenes, which may be difficult to distinguish from endogenous gene products. In situ hybridization will be key in these studies. Routine histopathologic and reporter gene analyses will be utilized, Dr. Rader, Principal Investigator of Project 3, will require the services of the Core for transgene detection as well as image analysis of large vessel for evidence of atherosclerosis.